Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enalapril, an angiotensin converting enzyme (ACE) inhibitor usually administered orally once daily, decreases blood pressure by lowering peripheral vascular resistance without increasing heart rate or output. It is effective in lowering blood pressure in all grades of essential and renovascular hypertension. Patients not responding adequately to enalapril monotherapy usually respond with the addition of a thiazide diuretic (or a calcium antagonist or beta-blocker), and rarely require a third antihypertensive agent. Enalapril is at least as effective as other established and newer ACE inhibitors, and members of other antihypertensive drug classes including diuretics, beta-blockers, calcium antagonists and alpha-blockers, but therapy with enalapril may be less frequently limited by serious adverse effects or treatment contraindications than with other drug classes. The most frequent adverse effect limiting all ACE inhibitor therapy in clinical practice is cough. This favourable profile of efficacy and tolerability, and the substantial weight of clinical experience, explain the increasing acceptance of enalapril as a major antihypertensive treatment and supports its use as logical first-line therapeutic option.
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PMID:Enalapril. A reappraisal of its pharmacology and therapeutic use in hypertension. 137 19

Idrapril is the prototype of a new chemical class of angiotensin converting enzyme (ACE) inhibitors, the hydroxamic non-amino acid derivatives. Idrapril strongly inhibited rat and human plasma ACE and rabbit lung ACE (IC50: 7-12 nM) as well as the pressor response induced by angiotensin I in anesthetized rats (ED50: 63 nmol/kg i.v.). Idrapril (0.04-23 mumol/kg i.v.) lowered the blood pressure dose dependently, up to 20-35%, in different models of hypertension (sodium-depleted spontaneously hypertensive rat, two-kidney-one-clip renal hypertensive rat, and aortic-coarctated rat), its profile being similar to that of captopril in terms of potency and efficacy. Idrapril and captopril reduced the blood pressure and potentiated substance P-induced bronchoconstriction in the guinea pig to the same extent, suggesting a similar degree of ACE inhibition in the circulation. However, idrapril potentiated capsaicin-induced bronchoconstriction (a model that has been related to the liability of ACE inhibitors to produce cough in patients) less effectively than captopril. We conclude that effective ACE inhibition in vitro and in vivo can be obtained with this novel class of compounds.
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PMID:Pharmacology of idrapril: a new class of angiotensin converting enzyme inhibitors. 138 23

1. A scheme for augmented spontaneous reporting of adverse drug events using advanced view data systems was developed and applied to study 67,698 consecutive patients prescribed captopril in general practice for the treatment of hypertension. 2. Captopril was an effective hypotensive agent in this population, as only 1.9% of patients were withdrawn because of apparent inefficacy. 3. Adverse effects of captopril resulted in withdrawal of treatment in 8.9% of recipients, and such effects were more frequent in elderly and female recipients. 4. Skin reactions--usually maculopapular rashes--tended to occur early during therapy whereas cough occurred much later and was reported more frequently in non-smokers. 5. Some 1.1% of recipients died during follow-up. There was no evidence of any unusual or unexpected causes of death which might be partially or totally captopril-related in the study cohort. 6. The study confirms the feasibility of large scale postmarketing surveillance studied in general practice and allowed risk benefit assessments to be made on the use of captopril for treating hypertension.
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PMID:Postmarketing surveillance of captopril for hypertension. 138 46

To assess the prevalence of cough as a side effect of angiotensin-converting enzyme inhibitor antihypertensive therapy, we reviewed 300 consecutive patient charts from a private practice and 200 consecutive patient charts from a university-based referral center for hypertension. Incidence of definite angiotensin-converting enzyme inhibitor-induced cough in the private practice was 25% and in the university practice, 7%, with an additional 6% of university-practice patients reporting a possible angiotensin-converting enzyme-inhibitor induced cough. This incidence is considerably greater than listed in the Physicians' Desk Reference. Reasons for the variability in incidence as reported in the literature are explored. Clinicians must be aware of this potentially disturbing side effect of angiotensin-converting enzyme inhibitors to avoid expensive and unnecessary diagnostic evaluations.
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PMID:Cough and ACE inhibitors. 844 19

The effect of hydrochlorothiazide, a diuretic which is used in the treatment not only of edema but also of hypertension, on coughs associated with treatment with enalapril was studied in guinea pigs. Chronic treatment with enalapril markedly and dose dependently enhanced the number of capsaicin-induced coughs. However, chronic treatment with hydrochlorothiazide significantly reduced the number of coughs associated with enalapril treatment, also in a dose-dependent manner. These results suggest that diuretics might be used to reduce the coughing associated with treatment with inhibitors of angiotensin-converting enzyme in patients with hypertension.
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PMID:The effect of hydrochlorothiazide on the enhanced coughing associated with treatment with enalapril. 149 49

During transesophageal echocardiography probe passage, airway reflexes are usually obtunded with topical local anesthetics. This technique meets with varying degrees of success. Even partially intact airway reflexes result in coughing, retching, and withdrawal, which may prevent transesophageal echocardiography examination or predispose to life-threatening tachycardia and hypertension. Proper preparation of the patient enhances comfort and helps protect against tachycardia and hypertension as well as reducing the time required for examination. This article outlines specific monitoring issues and offers precautions that are critical to transesophageal echocardiography probe passage. It suggests a premedication regimen and describes methods of sedation. Furthermore, it outlines the afferent innervation of the upper airway and specific techniques of temporary reflex interruption.
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PMID:Sensory blockade for difficult passage of transesophageal echocardiography probes. 151 Aug 53

Stevens-Johnson syndrome is an acute, inflammatory eruption of the skin and mucous membranes often associated with drug ingestion. A forty-five-year-old woman showed symptoms consistent with Stevens-Johnson syndrome two days after indapamide therapy was begun for the treatment of hypertension. Initial manifestations consisted of headaches, sore throat, cough, and symptoms of conjunctival injection, including redness and swelling. Approximately two weeks later, the patient noted skin eruptions involving the conjunctiva, lips, face, neck, trunk, and extremities. She was treated with cool compresses, antiseptics, ophthalmic antibiotics and steroids, and oral prednisone. Symptoms began to resolve approximately eight days after indapamide was discontinued and treatment was begun. Although rare, Stevens-Johnson syndrome should be considered in the differential diagnosis of a patient with a history of indapamide ingestion who presents with malaise, fever, and skin eruptions.
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PMID:Indapamide-associated Stevens-Johnson syndrome. 152 75

Cilazapril is a new once-daily angiotensin-converting (ACE) enzyme inhibitor which has been administered to 4,500 patients with mainly mild to moderate essential hypertension in a multinational clinical research program. Sitting diastolic blood pressure was reduced by about 9 mm Hg from baseline (p less than 0.01) after 4 weeks of treatment with cilazapril 1.25-10 mg/day in double-blind placebo-controlled studies. Total responder rates to cilazapril were usually 50-60% compared with 30% to placebo. Adding hydrochlorothiazide 12.5 mg/day to cilazapril 5.0 mg/day increased the total responder rate from 52 to 71%. Double-blind dose titration studies for 8 weeks showed that cilazapril 2.5-5 mg/day possessed equivalent efficacy to usual therapeutic regimens of sustained release propranolol, captopril, hydrochlorothiazide, atenolol and enalapril, Cilazapril did not affect heart rate. During long-term open administration for 52 weeks, or longer, cilazapril, either alone or in combination with hydrochlorothiazide, effectively maintained control of blood pressure. Treatment of patients with severe hypertension with cilazapril plus hydrochlorothiazide achieved a total responder rate of 73%. Adverse events were mostly observed within the first 8-16 weeks of treatment, with headache, dizziness, fatigue, nausea, cough and chest pain being the most frequent. Non-life-threatening angioedema, facial edema and mild hypotension occurred in less than or equal to 0.2% of patients, and orthostatic hypotension was reported in 2%. Abnormal laboratory test values were rarely found with cilazapril treatment. Of the 2.3% of patients with elevated serum creatinine, at any time point during the study and irrespective of outcome on continuation with cilazapril therapy, about two thirds had prior renal impairment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cilazapril: an overview of its efficacy and safety in hypertension. 153 34

The angiotensin converting enzyme (ACE) inhibitors are a group of effective drugs with a unique mechanism of action. These drugs have proven to be useful for hypertension and congestive heart failure. Early clinical trials of captopril used doses that are now known to be inappropriately high, and dose-related adverse effects were observed frequently. The recognition that lower doses are effective has reduced the incidence of adverse reactions and resulted in improved patient tolerance. When patients are properly selected and correctable risk factors are removed, serious side effects are uncommon. Unfortunately, the early reputation of nephrotoxicity persists, as does the belief that significant blood dyscrasias, endocrine effects and rash are serious risks for the average patient. After wide use of captopril, enalapril and lisinopril, and investigational trials of nearly a dozen newer agents, a sufficiency of clinical observation, experimental evidence and accurate postmarketing recording of events is accumulating to allow insight into the major toxicities with regard to more intelligent patient selection, more rational dosing and proper identification of risk factors. The most common adverse reactions are cough and skin rash. It appears that the agents are generally not cross-reactive with regard to skin rash, although it is not clear whether this effect is drug-specific or class-specific with regard to cough. Statistically but not clinically significant lowering of haemoglobin and hematocrit is common; these effects are inconsequential in most patients. Neutropenia, once thought to be prevalent, now appears to be so only in patients with autoimmune or collagen-vascular disease; the majority of patients outside these groups are at low risk. Hyperkalaemia is a frequent occurrence. This should not be surprising in view of the effect of the ACE inhibitors on plasma aldosterone. When dietary potassium intake is regulated and sources of altered potassium excretion are identified, hyperkalaemia is seldom a serious problem. Identification of sodium and water deficits allows correction before the drugs are started, and the frequency of hypotension and hyperkalaemia caused by the drugs is quite low if these factors are properly managed. An unexpected finding emerging in recent years is the dry cough associated with ACE inhibitor therapy. Its mechanism is not definitely known. Nonsteroidal anti-inflammatory drugs may control this symptom in some patients. The frequent observation of proteinuria in patients taking ACE inhibitors has gained notice and sometimes caused undue alarm. It is difficult to separate disease effects in diabetes and hypertension from true drug effects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Adverse effects of angiotensin converting enzyme (ACE) inhibitors. An update. 153 95

Angiotensin-converting enzyme (ACE) inhibitors are useful first-line drugs in the therapy of mild and moderate hypertension. Adverse reactions to this drug class are rarely serious. Hypotension, cough, rash, and taste disturbance are uncommon; reduced glomerular filtration and hyperkalemia occur infrequently; angioedema is rare and neutropenia is extremely rare. Quinapril is a new ACE inhibitor that is converted to biologically active quinaprilat in the liver. This ACE inhibitor has a rapid onset of action and inhibits local tissue converting enzyme systems in kidney, heart, and brain, as well as in the circulating renin-angiotensin system. Clinically significant adverse effects of quinapril occur at low rates. In 1,771 patients receiving quinapril, the reported incidence of the first occurrence of orthostatic hypotension was comparable to that seen in patients receiving placebo. In other studies, headache was reported by up to 4.7% of patients receiving quinapril, which is comparable to reported incidences of headache in patients receiving other ACE inhibitors. Other adverse events reported at rates greater than 1% include cough with associated rhinitis and bronchitis, dizziness, and somnolence. Such adverse events have only rarely led to the withdrawal of patients from clinical studies of quinapril.
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PMID:Adverse effects of angiotensin-converting enzyme inhibitors in antihypertensive therapy with focus on quinapril. 154 39


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